Exposure-response of ciclosporin and methotrexate in children and young people with severe atopic dermatitis: a secondary analysis of the TREatment of severe Atopic dermatitis Trial (TREAT)
- PMID: 40168525
- DOI: 10.1093/ced/llaf147
Exposure-response of ciclosporin and methotrexate in children and young people with severe atopic dermatitis: a secondary analysis of the TREatment of severe Atopic dermatitis Trial (TREAT)
Abstract
This is a secondary analysis of a multicentre randomized controlled trial of ciclosporin and methotrexate in children and young people (CYP) with severe atopic dermatitis (AD). Longitudinal trough ciclosporin and erythrocyte methotrexate polyglutamate (MTX-PG) concentrations were measured to evaluate their associations with treatment response and adverse events. Both ciclosporin (4 mg kg-1 daily) and methotrexate (0.4 mg kg-1 weekly) led to a significant reduction in disease severity scores over the 36-week treatment period. Higher trough ciclosporin concentrations were associated with lower disease severity scores and may serve as a useful tool for therapeutic drug monitoring of ciclosporin in CYP with AD. However, in contrast to a previously published study, steady-state erythrocyte-MTX-PG concentrations showed no significant association with treatment response. Drug concentrations were comparable between patients with and without drug-related adverse events.
© The Author(s) 2025. Published by Oxford University Press on behalf of British Association of Dermatologists.
Conflict of interest statement
Conflicts of interest: C.F. is Chief Investigator of the UK National Institute for Health Research-funded TREAT (ISRCTN15837754) and SOFTER (Clinicaltrials.gov: NCT03270566) trials as well as the UK-Irish Atopic eczema Systemic Therapy Register (A-STAR; ISRCTN11210918) and a Principle Investigator in the European Union (EU) Horizon 2020-funded BIOMAP Consortium (http://www.biomap-imi.eu/). He also leads the EU Trans-Foods consortium. His department has received investigator-led funding from Sanofi Genzyme and Pfizer for microbiome work. D.O.K. has received funding for advisory board participation with Sanofi Genzyme. M.W. is a steering committee member of the UK-Irish Atopic eczema Systemic Therapy Register (A-STAR; ISRCTN11210918). T.M. has received funding for advisory boards and teaching from Sanofi Genzyme, AbbVie and Pfizer. M.J.C. has received investigator-led funding from Hyphens Pharma, Johnson & Johnson, Sanofi, L’Oréal, Leo Pharma, ACO Nordic, Pfizer, Regeneron and Sanofi Genzyme, as well as funding for advisory board participation with Menlo. He has also received consultant fees from Boots, Eli Lilly and Procter & Gamble. S.J.B. is a medical adviser to the Ichthyosis Support Group and Eczema Outreach Support and has received funding from Wellcome. A.D.I. has received consulting fees from Area, Almirall, AbbVie, Pfizer, Eli Lilly and Sanofi Regeneron and is the Director of the International Eczema Council. P.B. has received funding for advisory board participation with AbbVie and speaker fees from Pfizer. She is a steering committee member of the UK-Irish Atopic eczema Systemic Therapy Register (A-STAR; ISRCTN11210918) and a medical adviser for the National Eczema Society. S.J.B. has received research funding (but no personal financial benefits) from Wellcome (220875/Z/20/Z), UK Research and Innovation, Medical Research Council, Rosetrees Trust, Stoneygates Trust, British Skin Foundation, Charles Wolfson Charitable Trust, anonymous donations from individuals with eczema, Unilever, Pfizer, AbbVie, Sosei-Heptares, Janssen, European Lead Factory (multiple industry partners) and the BIOMAP Consortium (EC-IMI project ref. no. 821511). T.H.S. was part-funded through an NIHR Career Development Fellowship (CDF-2014-07-006) at the start of the study. T.H.S. is a member of the UK Dermatology Clinical Trials Network Steering Committee and was chair of the NIHR Research for Patient Benefit East of England Research Advisory Committee between 1 January 2020 and 31 December 2023. T.H.S. was also a member of the following NIHR funding committees: HTA Additional Capacity Funding Board (no dates given); HTA Antimicrobial Resistance Themed Call Board, 10 December 2013 to 3 June 2014; HTA Efficient Study Designs – 2, 1 November 2015 to 31 July 2016; HTA Efficient Study Designs Board, 13 October 2014 to 17 December 2014; HTA End of Life Care and Add-on Studies, 1 September 2015 to 9 February 2016; HTA Primary Care Themed Call board, 17 September 2013 to 18 February 2014; HTA General Committee, 1 August 2016 to 31 July 2017; and HTA Commissioning Committee, 19 June 2017 to 31 December 2019. The other authors declare no conflicts of interest.
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